Association of an intragenic microsatellite marker in the CC16 gene with asthma in the Indian population

Sharma, Shilpy; Ghosh, Balaram

doi:10.1007/s10038-004-0206-8

Cited by 17 publications

(16 citation statements)

References 34 publications

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“…The effects of genetic variants in or near the CC16 and SP-D coding genes on circulating levels of their respective proteins have been previously reported (19,44,45) and the genetic variants in corresponding genes were also listed among the top SNPs in our study. However, there were remote genetic loci affecting the levels of CC16 and SP-D, which have no significant linkage disequilibrium with SNPs in the biomarker coding genes.…”

Section: Discussionsupporting

confidence: 52%

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Kim

Cho

Hersh

et al. 2012

Am J Respir Crit Care Med

113

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Rationale: A genome-wide association study (GWAS) for circulating chronic obstructive pulmonary disease (COPD) biomarkers could identify genetic determinants of biomarker levels and COPD susceptibility. Objectives: To identify genetic variants of circulating protein biomarkers and novel genetic determinants of COPD. Methods: GWAS was performed for two pneumoproteins, Clara cell secretory protein (CC16) and surfactant protein D (SP-D), and five systemic inflammatory markers (C-reactive protein, fibrinogen, IL-6, IL-8, and tumor necrosis factor-a) in 1,951 subjects with COPD. For genome-wide significant single nucleotide polymorphisms (SNPs) (P , 1 3 10 28 ), association with COPD susceptibility was tested in 2,939 cases with COPD and 1,380 smoking control subjects. The association of candidate SNPs with mRNA expression in induced sputum was also elucidated. Measurements and Main Results: Genome-wide significant susceptibility loci affecting biomarker levels were found only for the two pneumoproteins. Two discrete loci affecting CC16, one region near the CC16 coding gene (SCGB1A1) on chromosome 11 and another locus approximately 25 Mb away from SCGB1A1, were identified, whereas multiple SNPs on chromosomes 6 and 16, in addition to SNPs near SFTPD, had genome-wide significant associations with SP-D levels. Several SNPs affecting circulating CC16 levels were significantly associated with sputum mRNA expression of SCGB1A1 (P ¼ 0.009-0.03). Several SNPs highly associated with CC16 or SP-D levels were nominally associated with COPD in a collaborative GWAS (P ¼ 0.001-0.049), although these COPD associations were not replicated in two additional cohorts. Conclusions: Distant genetic loci and biomarker-coding genes affect circulating levels of COPD-related pneumoproteins. A subset of these protein quantitative trait loci may influence their gene expression in the lung and/or COPD susceptibility. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).

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Section: Discussionsupporting

confidence: 52%

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Kim

Cho

Hersh

et al. 2012

Am J Respir Crit Care Med

113

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“…The associations between the risk of asthma and gene polymorphisms, such as single nucleotide polymorphism (SNPs), have been studied extensively. Recently, a number of studies have investigated the association between the risk of asthma and the CC16 gene A38G polymorphism (6)(7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

CC16 Gene A38G Polymorphism and Susceptibility to Asthma: An Updated Meta-analysis

Cheng

Xue

et al. 2015

Intern. Med.

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Objective To comprehensively evaluate the association between the CC16 gene A38G polymorphism and the risk of asthma. Methods Studies were retrieved from databases including PubMed, EMBASE, Web of Science and the Chinese Biomedical Literature Database according to the inclusive and exclusive criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Materials Fifteen case-control studies with 1,623 cases and 3,294 controls were recruited for the analysis of the association between the CC16 gene A38G polymorphism and the risk of asthma.

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“…Recent studies on humans and rats have shown that CC16 is a sensitive biomarker of respiratory epithelial injury in exposures to welder fumes, glutaraldehyde, nitric oxides, or Al foundry dusts [18][19][20][21][22][23]. Clara cell proteins are involved in the pathogenic mechanisms leading to fibrosis [15,24], chronic obstructive pulmonary disease (COPD) [25,26], and asthma in humans [27][28][29] and in murine asthma model [30,31]. Low level of CC16 was observed in serum and bronchoalveolar lavage fluid (BAL) of active smokers [32].…”

Section: Introductionmentioning

confidence: 99%

Serum Clara Cell Protein as an Indicator of Pulmonary Impairment in Occupational Exposure at Aluminum Foundry

Hałatek¹,

Trzcinka-Ochocka²,

Matczak³

et al. 2006

International Journal of Occupational Medicine and Environmental Health

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Objectives: Although some of the exposures in aluminum (Al) smelting have been well characterized, and respiratory disorders in aluminum production workers are well known, the relationship between internal aluminum loads and appropriate lung biomarkers have not been elucidated. The aim of our work was to carry out a comprehensive investigation in workers employed in the Aluminum Foundry Casting Department with special reference to currently existing hygiene standards, known as threshold limit values (TLV) based on aluminum effects on the respiratory system. The measurement of serum anti-inflammatory Clara cell protein (CC16) was employed as a peripheral marker of the lung epithelium function. Materials and Methods: A group of 50 casting smelters, 5 locksmiths, 11 sawyers and auxiliary workers exposed to dust containing 14% of aluminum, and a group of 42 controls were examined. Respiratory function tests were performed and forced volume capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), forced expiratory volume in the first percent (FEV 1 %), forced expiratory flows in 50% VC (FEV 50 ), and markers of foundry workers' exposure and body burden, Al concentration in the breathing zone, blood and urine, biomarkers of the effects of exposure, concentration of CC16 and hyaluronic acid (HA) in serum were determined in all examined workers. Additional measurements comprised determinations of serum iron (Fe) levels, myeloperoxidase (MPO), eosinophil cationic protein (ECP), immunoglobulin E (IgE), glutathione S-transferase (GST), and superoxide dismutase (SOD) activity in erythrocytes. Results: The group of casting smelters was characterized by the highest levels of aluminum in urine (Al-U) (43.7 mg L -1 ), high levels of MPO, ECP and IgE, high SOD activity, low CC16 levels, and low activity of GST. Lower Al-U excretion was observed in locksmiths (35.2 mg L -1 ) and sawyers (21.7 mg L -1 ). Serum CC16 proved to be the most sensitive biomarker, showing high inverse relationship with serum Al (Al-S) concentrations in casting smelters (p = 0.006). Conclusions: The study showed that in conditions of occupational exposure, dusts containing Al 2 O 3 < 1 mg m -3 cause changes in the respiratory system and biomarkers in serum, especially in CC16, connected with altered functioning of this system. Changes in concentrations of the examined biomarkers and also in respiratory parameters of the study subjects were observed when Al-U concentration was > 40 mg L -1 .

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Association of an intragenic microsatellite marker in the CC16 gene with asthma in the Indian population

Cited by 17 publications

References 34 publications

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

Genome-Wide Association Analysis of Blood Biomarkers in Chronic Obstructive Pulmonary Disease

CC16 Gene A38G Polymorphism and Susceptibility to Asthma: An Updated Meta-analysis

Serum Clara Cell Protein as an Indicator of Pulmonary Impairment in Occupational Exposure at Aluminum Foundry

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